Adolescent pre‐exposure to ethanol and 3,4‐methylenedioxymethylamphetamine (MDMA) increases conditioned rewarding effects of MDMA and drug‐induced reinstatement
Addiction Biology – October 13, 2011
Source: OpenAlex
Summary
Repeated exposure to ethanol (EtOH) and MDMA during adolescence significantly enhances the addictive properties of MDMA. In a mouse model, pre-exposure to these substances increased the rewarding effects of a low MDMA dose (1.25 mg/kg) and led to more persistent conditioned place preference (CPP). Notably, reinstatement of CPP occurred with lower priming doses (1.25 mg/kg for EtOH or MDMA alone) after extinction. Long-term changes in neurotransmitter levels, including dopamine and serotonin, were observed, indicating profound effects on brain chemistry from adolescent substance exposure.
Abstract
ABSTRACT Many adolescents often take ethanol (EtOH) in combination with 3,4‐methylenedioxymethylamphetamine (MDMA). In the present work, we used a mouse model to study the effect of repeated pre‐exposure during adolescence to EtOH (2 g/kg), MDMA (10 or 20 mg/kg) or EtOH + MDMA on the rewarding and reinstating effects of MDMA in the conditioned place preference (CPP) paradigm. Pre‐exposure to EtOH, MDMA or both increased the rewarding effects of a low dose of MDMA (1.25 mg/kg). These pre‐treatments did not affect the acquisition of the CPP induced by 5 mg/kg of MDMA. However, the CPP was more persistent in mice pre‐exposed to both doses of MDMA or to EtOH + MDMA20. After extinction of the CPP induced by 5 mg/kg of MDMA, reinstatement was observed in all groups with a priming dose of 2.5 mg/kg of MDMA, in the groups pre‐exposed to EtOH or MDMA alone with a priming dose of 1.25 mg/kg, and in the groups pre‐treated with MDMA alone with a priming dose of 0.625 mg/kg. Pre‐treatment during adolescence with MDMA or EtOH induced long‐term changes in the level of biogenic amines [dihydroxyphenyl acetic acid, homovanillic acid, dopamine turnover, serotonin (5‐hydroxytryptamine, 5‐HT) and 5‐hydroxyindole acetic acid (5‐HIAA) in the striatum, and 5‐HT and 5‐HIAA in the cortex] after the first reinstatement test, although these effects depended on the dose used during conditioning. These results suggest that exposure to EtOH and MDMA during adolescence reinforces the addictive properties of MDMA.